NIMOTOP IV

Indications

• Prevention of ischemic neurological defects following aneurysmal subarachnoid hemorrhage

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: 60 mg every 4 hours, to be started within 4 days of aneurysmal subarachnoid hemorrhage and continued for 21 days.

Mechanism of action

Nimodipine blocks the intracellular influx of calcium through voltage-dependent and receptor-operated slow calcium channels across myocardial, vascular smooth muscle, and neuronal cells. It specifically binds to L-type voltage-gated calcium channels, inhibiting calcium ion transfer, and thus preventing vascular smooth muscle contraction. This mechanism aids in dilating cerebral blood vessels and preventing calcium overload in neurons, contributing to its efficacy in subarachnoid hemorrhage.

Pharmacodynamics

As a calcium channel blocker, nimodipine reduces the incidence and severity of ischemic neurological deficits in patients with subarachnoid hemorrhage. Its primary action involves inhibiting calcium ion transfer into smooth muscle cells, thereby preventing contractions. Nimodipine demonstrates a preferential effect on cerebral arteries, likely due to its lipophilicity, which allows it to cross the blood-brain barrier effectively.

Pharmacokinetics

Nimodipine is well absorbed after oral administration, with a bioavailability of approximately 13% due to extensive first-pass metabolism. The drug is highly protein-bound (95-97%) and is metabolized primarily in the liver by cytochrome P450 enzymes. The elimination half-life is about 1-2 hours, and it is excreted mainly as metabolites in urine. Its pharmacokinetics may be altered by liver function, and dosages may need adjustment in patients with hepatic impairment.

Contra-indications

• Hypersensitivity to nimodipine or any of its excipients
• Severe hypotension
• Severe aortic stenosis

Adverse effects

• Hypotension
• Dizziness
• Headache
• Nausea
• Vomiting
• Flushing
• Tachycardia
• Dyspnoea
• Skin reactions
• Fever
• Angioedema

Interactions

• Enzalutamide: Moderate (decreases exposure)
• Apalutamide: Moderate (decreases exposure)
• Dronedarone: Moderate (increases exposure)
• Valproate: Moderate (increases exposure)
• Azole antifungals: Moderate (increases exposure)
• Miconazole: Moderate (increases exposure)
• Cobicistat: Moderate (increases exposure)
• Crizotinib: Moderate (increases exposure)
• Dabrafenib: Moderate (decreases exposure)
• Idelalisib: Moderate (increases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Monitor blood pressure regularly during treatment
• Risk of thrombosis in patients with certain conditions
• Pregnancy and lactation considerations

Pregnancy

Nimodipine is classified as category C. Animal reproduction studies have shown adverse effects, but there are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether nimodipine is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

Store at room temperature, away from moisture and heat. Protect from light. Do not freeze.

Formulations

• Capsules: 30 mg
• Injection: 1 mg/ml in 20 ml vials for intravenous infusion

Mechanism of action

Although the precise mechanism of action is not known, nimodipine blocks intracellular influx of calcium through voltage-dependent and receptor-operated slow calcium channels across the membranes of myocardial, vascular smooth muscle, and neuronal cells. By specifically binding to L-type voltage-gated calcium channels, nimodipine inhibits the calcium ion transfer, resulting in the inhibition of vascular smooth muscle contraction. Evidence suggests that the dilation of small cerebral resistance vessels, with a resultant increase in collateral circulation, and/or a direct effect involving the prevention of calcium overload in neurons may be responsible for nimodipine's clinical effect in patients with subarachnoid hemorrhage.

Pharmacodynamics

Nimodipine belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured congenital aneurysms who are in good neurological condition post-ictus (e.g., Hunt and Hess Grades I-III). The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood brain barrier.